The primary goal of the proposed research is to determine the role that alteration in membrane lipid components play in cardiac mitochondrial function. Subsarcolemmal and interfibrillar heart mitochondria will be separately analyzed since these two mitochondrial types differ not only in their respective locations in the cell, but also in response to pathological insult. A Ca++ independent phospholipase A1 which is active during incubation of subsarcolemmal but not interfibrillar heart mitochondria will be characterized as to substrate specificity, submitochondrial location, product formation and regulatory properties. The role that the products of this activity, include lysophospholipids and free fatty acids, play in the greater membrane permeability of subsarcolemmal mitochondria will be studied. The enzyme will be isolated by affinity chromatography and characterized in defined lipid environments. Alterations in the respiratory capacity of subsarcolemmal, but not interfibrillar heart mitochondria have been described in ischemic tissue and hearts from glucagon-injected animals. The role that minor lipid components, namely lysophosphatidylethanolamine and free fatty acids, as well as phospholipases play in these effects will be investigated. It is the long range goal of this proposal to be able to manipulate lipolytic activities in the intact heart in order to preserve mitochondria function and, in essence, cardiac viability in a variety of disease states.